RESUMO
Telephone call intervention did not improve alendronate persistence in Fracture Liaison Service (FLS) patients in this study. A bone turnover marker cut-off point for alendronate persistence is proposed for individual FLS patients. INTRODUCTION: FLS aims to prevent subsequent fractures, which should include improving patients' persistence with prescribed oral bisphosphonates. We studied the influence of telephone calls and the predictive value of changes in bone turnover markers (BTMs) for evaluating persistence with alendronate. METHODS: Postmenopausal women with a recent fracture and osteoporosis who started alendronate were randomized to receive three phone calls (PC) (after 1, 4, and 12 months) or no phone calls (no PC). s-CTX and P1NP were measured at baseline and after 3, 6, 9, and 12 months. As a reference group, 30 postmenopausal osteopenic patients with a recent fracture were analyzed as well. Persistence was assessed using the Dutch National Switch Point Pharmacies-GPs database and cross-referenced with PC, no PC, and BTM changes. Cut-off values of BTMs were calculated based on least significant change (LSC) and also on underrunning median values of the untreated osteopenic postmenopausal reference group with a recent fracture. RESULTS: Out of 119 patients, 93 (78%) completed 12 months follow-up (45 PC and 48 no PC). Mean age was 69 years. Persistence was similar in PC and no PC participants. The cut-off value > 29% (< 415 ng/L) as LSC of s-CTX and > 36% (< 53.1 µg/L) as LSC of P1NP was determined optimally showing alendronate persistence after 1 year (being 93 and 88%, respectively). CONCLUSIONS: In this context, telephone calls did not improve persistence. In around 90% of patients, 1-year alendronate persistence was confirmed by achieving LSC of s-CTX and of P1NP at 12 months.
Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Monitoramento de Medicamentos/métodos , Adesão à Medicação/estatística & dados numéricos , Osteoporose Pós-Menopausa/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Absorciometria de Fóton , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Densidade Óssea/efeitos dos fármacos , Densidade Óssea/fisiologia , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/farmacologia , Remodelação Óssea/efeitos dos fármacos , Remodelação Óssea/fisiologia , Difosfonatos/administração & dosagem , Difosfonatos/farmacologia , Feminino , Humanos , Pessoa de Meia-Idade , Países Baixos , Osteoporose Pós-Menopausa/fisiopatologia , TelefoneRESUMO
PURPOSE: Sufficient vitamin D status may be defined as the evolutionary established circulating 25-hydroxyvitamin D [25(OH)D] matching our Paleolithic genome. METHODS: We studied serum 25(OH)D [defined as 25(OH)D2 + 25(OH)D3] and its determinants in 5 East African ethnical groups across the life cycle: Maasai (MA) and Hadzabe (HA) with traditional life styles and low fish intakes, and people from Same (SA; intermediate fish), Sengerema (SE; high fish), and Ukerewe (UK; high fish). Samples derived from non-pregnant adults (MA, HA, SE), pregnant women (MA, SA, SE), mother-infant couples at delivery (UK), infants at delivery and their lactating mothers at 3 days (MA, SA, SE), and lactating mothers at 3 months postpartum (SA, SE). Erythrocyte docosahexaenoic acid (RBC-DHA) was determined as a proxy for fish intake. RESULTS: The mean ± SD 25(OH)D of non-pregnant adults and cord serum were 106.8 ± 28.4 and 79.9 ± 26.4 nmol/L, respectively. Pregnancy, delivery, ethnicity (which we used as a proxy for sunlight exposure), RBC-DHA, and age were the determinants of 25(OH)D. 25(OH)D increased slightly with age. RBC-DHA was positively related to 25(OH)D, notably 25(OH)D2. Pregnant MA (147.7 vs. 118.3) and SE (141.9 vs. 89.0) had higher 25(OH)D than non-pregnant counterparts (MA, SE). Infant 25(OH)D at delivery in Ukerewe was about 65 % of maternal 25(OH)D. CONCLUSIONS: Our ancient 25(OH)D amounted to about 115 nmol/L and sunlight exposure, rather than fish intake, was the principal determinant. The fetoplacental unit was exposed to high 25(OH)D, possibly by maternal vitamin D mobilization from adipose tissue, reduced insulin sensitivity, trapping by vitamin D-binding protein, diminished deactivation, or some combination.
Assuntos
25-Hidroxivitamina D 2/sangue , Calcifediol/sangue , Dieta/efeitos adversos , Estilo de Vida , Estado Nutricional , Deficiência de Vitamina D/sangue , Adulto , Animais , Biomarcadores/sangue , População Negra , Dieta/etnologia , Exposição Ambiental , Feminino , Sangue Fetal , Humanos , Recém-Nascido , Lactação/sangue , Estilo de Vida/etnologia , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Estado Nutricional/etnologia , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/etnologia , Complicações na Gravidez/etiologia , Luz Solar , Tanzânia , Deficiência de Vitamina D/etnologia , Deficiência de Vitamina D/etiologia , Deficiência de Vitamina D/prevenção & controleRESUMO
OBJECTIVE: Curaçao (12 degrees 10ON, 69 degrees OW) is characterized by whole year abundant sunshine (8-10 hours/day). We challenged the automatic assumption that people living in tropical countries do not have a high risk of vitamin D deficiency, and investigated the vitamin D status in a tropical environment. METHODS: For this, we selected fifty-two elderly people with little or no exposure to direct sunlight [median 84 (60-96) years; 34females, 18 males] and who were cared for by community nurses or lived in retirement or nursing homes. Furthermore, six rehabilitating orthopaedic patients [median 72 (38-90) years; one female, five males] were included. Serum 25(OH)D, calcium, phosphate, parathyroid hormone (PTH) and creatinine were measured. Those exhibiting elevated creatinine, PTH or both had their 1,25-dihydroxyvitamin D [1,25(OH)2D] examined. RESULTS: Serum levels of 25(OH)D below 25, 50 and 75 nmol/L were detected in, respectively, seven (12%), 22 (38%) and 48 (83%) ofthe fifty-eight persons. Four persons had combined high creatinine and PTH, and low 1,25(OH)2D, which was not known by their caregivers. CONCLUSION: Abundant sunshine outdoors is no guarantee for vitamin D sufficiency. More attention is needed for vitamin D deficiency in risk groups living in tropical areas and elderly persons with poor kidney function.
Assuntos
Luz Solar , Deficiência de Vitamina D/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Calcitriol/sangue , Cálcio/sangue , Creatinina/sangue , Feminino , Serviços de Assistência Domiciliar , Instituição de Longa Permanência para Idosos , Humanos , Masculino , Pessoa de Meia-Idade , Antilhas Holandesas/epidemiologia , Casas de Saúde , Hormônio Paratireóideo/sangue , Fosfatos/sangue , Centros de Reabilitação , Risco , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangueRESUMO
BACKGROUND: Indolent systemic mastocytosis (ISM) is a rare disease characterized by accumulation of abnormal mast cells in various tissues, including bone marrow. Symptoms are usually related to release of mast cell mediators. The aims are to establish the prevalence of osteoporotic fractures in ISM and to investigate the association with serum tryptase and the urinary histamine metabolites, methylhistamine (MH), and methylimidazole acetic acid. METHODS: The fracture prevalence in 157 patients (65 men; 92 women), mean age 54 ± 12 years, was assessed by vertebral morphometry and data from patient records, supplemented by a questionnaire. Bone mineral density (BMD) of lumbar spine and femoral neck was measured, and tryptase and histamine metabolites were analysed. RESULTS: We registered 235 lifetime fractures in 154 patients, including 140 osteoporotic (low-energy trauma) fractures, of which 62% were vertebral, 1% hip and 36% other nonvertebral fractures. Osteoporotic fractures and osteoporosis were found in 37% and 28% of the patients, respectively. In men, the prevalence of these osteoporotic manifestations (46% <50 years; 73% ≥50 years) was much higher compared with women (18% <50 years; 58% ≥50 years). Older age, male gender, and higher urinary MH were independently related to the osteoporotic manifestations. CONCLUSIONS: This first publication about prevalence of fractures and osteoporosis in patients with ISM shows that the risk of osteoporotic fractures is high, especially in men. Higher urinary MH levels are associated with a higher risk of osteoporotic manifestations. Routine measurements of BMD and vertebral morphometry are warranted in these patients for early detection of osteoporosis.
Assuntos
Fraturas Ósseas/epidemiologia , Osteoporose/epidemiologia , Triptases/sangue , Adulto , Idoso , Densidade Óssea , Feminino , Colo do Fêmur/diagnóstico por imagem , Fraturas Ósseas/diagnóstico por imagem , Histamina/metabolismo , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Mastocitose Sistêmica/diagnóstico por imagem , Mastocitose Sistêmica/epidemiologia , Mastocitose Sistêmica/fisiopatologia , Pessoa de Meia-Idade , Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/epidemiologia , Prevalência , Radiografia , Coluna VertebralRESUMO
BACKGROUND: Risk indicators of indolent systemic mastocytosis (ISM) in adults with clinical suspicion of ISM without accompanying skin lesions [urticaria pigmentosa (UP)] are lacking. This study aimed at creating a decision tree using clinical characteristics, serum tryptase, and the urinary histamine metabolites methylimidazole acetic acid (MIMA) and methylhistamine (MH) to select patients for bone marrow investigations to diagnose ISM. METHODS: Retrospective data analysis of all adults, in whom bone marrow investigations were performed to diagnose ISM, was carried out. RESULTS: In total, 142 patients were included. SM was absent in all 44 patients with tryptase <10 µg/l, in 45 of 98 (46%) patients with tryptase ≥10 µg/l and in 18 of 52 patients (35%) with tryptase >20 µg/l. Above 43 µg/l, all patients had ISM (n = 11). Male gender, insect venom anaphylaxis as presenting symptom, tryptase, MIMA, and MH were independent ISM predictors. If tryptase was ≥10 µg/l, the diagnostic accuracy of MIMA and MH was high (areas under the ROC curve 0.92). CONCLUSIONS: In suspected patients without UP, the ISM risk is very low (if present at all) if tryptase is <10 µg/l. If tryptase is ≥10 µg/l, this risk depends on MIMA and MH, being low if these are normal, but high if these are elevated. Male gender and insect venom anaphylaxis are additional risk indicators. We recommend refraining from bone marrow examinations in suspected patients without UP if tryptase is <10 µg/l. Our results question the reliability of the minor diagnostic World Health Organization criterion of tryptase >20 µg/l.
Assuntos
Imidazóis/urina , Mastocitose Sistêmica/complicações , Mastocitose Sistêmica/diagnóstico , Metilistaminas/urina , Triptases/sangue , Urticaria Pigmentosa/complicações , Adulto , Medula Óssea/metabolismo , Medula Óssea/patologia , Feminino , Histamina/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , RiscoRESUMO
SUMMARY: Osteoporosis is a well recognized complication of ankylosing spondylitis (AS). This study indicates that increased bone turnover, inflammation, and low vitamin D levels are important in the pathophysiology of AS-related osteoporosis, and that bone turnover markers (BTM) are valuable markers to detect bone loss in AS. INTRODUCTION: The aim of this study was to elucidate the pathophysiology of AS-related osteoporosis by investigating the relation between bone mineral density (BMD), BTM, vitamin D, and clinical assessments of disease activity and physical function, as well as to identify parameters that are related to low BMD (osteopenia or osteoporosis) in AS patients with active disease. METHODS: One hundred twenty-eight consecutive Dutch AS outpatients were included in this cross-sectional study. Bath AS Disease Activity Index (BASDAI), erythrocyte sedimentation rate (ESR), C-reactive protein, ASAS-endorsed disease activity score (ASDAS), Bath AS Functional Index (BASFI), bone formation markers procollagen type 1 N-terminal peptide (PINP) and osteocalcin (OC), bone resorption marker serum C-telopeptides of type I collagen (sCTX), 25-hydroxyvitamin D (25OHvitD), lumbar spine and hip BMD, and vertebral fractures were assessed. Z-scores of BTM were calculated using matched 10-year cohorts of a Dutch reference group to correct for the normal influence that age and gender have on bone turnover. RESULTS: sCTX Z-score, OC Z-score, BASDAI, age, and gender were independently related to low BMD. In addition, PINP Z-score, ESR, 25OHvitD, age, and gender were independently related to sCTX and/or OC Z-score. CONCLUSIONS: This study indicates that increased bone turnover, inflammation, and low vitamin D levels are important in the pathophysiology of AS-related osteoporosis. Furthermore, sCTX and OC Z-scores seem to be valuable markers to detect bone loss in AS patients in daily clinical practice where BMD of the lumbar spine, measured by DXA, may be overestimated due to osteoproliferation in patients with advanced AS.
Assuntos
Osteoporose/etiologia , Espondilite Anquilosante/complicações , Vitamina D/análogos & derivados , Adulto , Biomarcadores/sangue , Densidade Óssea/fisiologia , Remodelação Óssea/fisiologia , Colágeno Tipo I/sangue , Estudos Transversais , Feminino , Articulação do Quadril/fisiopatologia , Humanos , Vértebras Lombares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Osteoporose/sangue , Osteoporose/fisiopatologia , Peptídeos/sangue , Fatores de Risco , Fraturas da Coluna Vertebral/sangue , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/fisiopatologia , Espondilite Anquilosante/sangue , Espondilite Anquilosante/fisiopatologia , Vitamina D/sangueRESUMO
BACKGROUND: Mitochondrial disease is a rare, hereditary disease with a heterogeneous clinical presentation. However, fatigue is a common and burdensome complaint in children and adolescents with mitochondrial disease. No psychological intervention targeting fatigue exists for paediatric patients with a mitochondrial disease. We designed the PowerMe intervention, a blended cognitive behaviour therapy targeting fatigue in children and adolescents with mitochondrial disease. The aim of the intervention is to reduce perceived fatigue by targeting fatigue-related cognitions and behaviours. METHODS: A multiple baseline single case experiment will be conducted in five children (8-12 years old) and 5 adolescents (12-18 years old) with mitochondrial disease and severe fatigue. Patients will be included in the study for 33 weeks, answering weekly questions about the fatigue. Patients will be randomly assigned a baseline period of 5 to 9 weeks before starting the PowerMe intervention. The intervention consists of face-to-face and online sessions with a therapist and a website with information and assignments. The treatment will be tailored to the individual. Each patient will work on their personalized treatment plan focusing on personally relevant goals. The primary outcome is perceived fatigue. Secondary outcomes are quality of life, school presence and physical functioning. DISCUSSION: The results of the PowerMe study will provide information on the efficacy of a blended cognitive behaviour therapy on reducing perceived fatigue and its impact on daily life in children and adolescents with mitochondrial disease. Strengths and limitations of the study design are discussed. TRIAL REGISTRATION: Dutch Trial Register NTR 7675. Registered on 17 December 2018. Identifier https://www.trialregister.nl/trial/7433.
Assuntos
Terapia Cognitivo-Comportamental , Doenças Mitocondriais , Adolescente , Criança , Fadiga/diagnóstico , Fadiga/terapia , Humanos , Doenças Mitocondriais/diagnóstico , Doenças Mitocondriais/terapia , Qualidade de Vida , Projetos de PesquisaRESUMO
Cardiovascular disease (CVD) is a leading cause of mortality in renal transplant recipients (RTRs). Metabolic syndrome (MS) is highly prevalent in RTRs. Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic component of MS. We investigated associations of NAFLD markers with MS and mortality. RTRs were investigated between 2001 and 2003. NAFLD markers, alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT) and alkaline phosphatase (AP) were measured. Bone and nonbone fractions of AP were also determined. Death was recorded until August 2007. Six hundred and two RTRs were studied (age 52+/-12 years, 55% men). At baseline 388 RTRs had MS. Prevalence of MS was positively associated with liver enzymes. During follow-up for 5.3[4.5-5.7] years, 95 recipients died (49 cardiovascular). In univariate Cox regression analyses, GGT (HR=1.43[1.21-1.69], p<0.001) and AP (HR=1.34[1.11-1.63], p=0.003) were associated with mortality, whereas ALT was not. Similar associations were found for cardiovascular mortality. Adjustment for potential confounders, including MS, diabetes and traditional risk factors did not materially change these associations. Results for nonbone AP mirrored that for total AP. ALT, GGT and AP are associated with MS. Of these three enzymes, GGT and AP are associated with mortality, independent of MS. These findings suggest that GGT and AP are independently related to mortality in RTRs.
Assuntos
Fígado Gorduroso/complicações , Transplante de Rim/mortalidade , Síndrome Metabólica/complicações , Adulto , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Biomarcadores/sangue , Estudos de Coortes , Fígado Gorduroso/sangue , Fígado Gorduroso/enzimologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Transplante de Rim/efeitos adversos , Transplante de Rim/fisiologia , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/enzimologia , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , gama-Glutamiltransferase/sangueRESUMO
The systemic pro-inflammatory state present in patients with rheumatoid arthritis (RA) accelerates the progression of atherosclerosis through chronic endothelial activation. Uncoupling of endothelial nitric oxide synthase plays a central role in the amplification of oxidative signalling pathways that chronically activate and, ultimately, injure the endothelium. Recent studies indicate that the resultant loss of endothelial integrity in patients with RA may also involve defects in the vascular regenerative potential provided by circulating endothelial progenitor cells (EPC). This is most likely the consequence of endothelial cell dysfunction in the bone marrow stroma, which hampers the mobilisation of these EPC to the circulation. In addition, mediators of systemic inflammation in RA can affect a second pathway of vascular regeneration. Under normal circumstances, myeloid CD14+ cells can adopt a pro-angiogenic phenotype that plays a key role in vascular remodelling and collateral formation. However, the chronic systemic inflammation observed in patients with RA may skew the differentiation of bone marrow and circulating CD14+ cells in such a way that these cells lose their capacity to support collateral formation, increasing the risk of cardiovascular disease. Taken together, in patients with RA, the impaired capacity of circulating cells to support vascular regeneration may comprise a novel pathway in the development of premature atherosclerosis.
Assuntos
Artrite Reumatoide/fisiopatologia , Mediadores da Inflamação/fisiologia , Circulação Colateral/fisiologia , Endotélio Vascular/fisiopatologia , Humanos , Células Progenitoras Mieloides/fisiologia , Regeneração/fisiologiaRESUMO
OBJECTIVES: To investigate the influence of antibody formation to TNF-α blocking agents on the clinical response in AS patients treated with infliximab (IFX), etanercept (ETA), or adalimumab (ADA), and to investigate the development of ANA, ANCA, and anti-dsDNA antibodies in association with the formation of antibodies to TNF-α blocking agents. METHODS: Consecutive AS outpatients with active disease who started treatment with IFX (n=20), ETA (n=20), or ADA (n=20) were included in this longitudinal observational study. Clinical data were collected prospectively at baseline and after 3, 6, and 12 months of anti-TNF-α treatment. At the same time points, serum samples were collected. In these samples, antibodies to TNF-α blocking agents, serum TNF-α blocker levels, and ANA, ANCA, and anti-dsDNA antibodies were measured retrospectively. RESULTS: Anti-IFX, anti-ETA, and anti-ADA antibodies were induced in 20%, 0%, and 30% of patients, respectively. Although ANA, ANCA, and anti-dsDNA antibodies were detected during anti-TNF-α treatment, no significant association was found between the presence of these autoantibodies and the formation of antibodies to TNF-α blocking agents. Patients with anti-IFX or anti-ADA antibodies had significantly lower serum TNF-α blocker levels compared to patients without these antibodies. Furthermore, significant negative correlations were found between serum TNF-α blocker levels and assessments of disease activity. CONCLUSIONS: This study indicates that antibody formation to IFX or ADA is related to a decrease in efficacy and early discontinuation of anti-TNF-α treatment in AS patients. Furthermore, autoantibody formation does not seem to be associated with antibody formation to TNF-α blocking agents.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Autoanticorpos/imunologia , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/imunologia , Fator de Necrose Tumoral alfa/imunologia , Adalimumab , Adulto , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais Humanizados , Antirreumáticos/imunologia , Etanercepte , Feminino , Nível de Saúde , Humanos , Imunoglobulina G/imunologia , Imunoglobulina G/uso terapêutico , Infliximab , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Receptores do Fator de Necrose Tumoral/imunologia , Receptores do Fator de Necrose Tumoral/uso terapêutico , Índice de Gravidade de Doença , Espondilite Anquilosante/fisiopatologiaRESUMO
The central dogma in molecular biology states that genetic information is transmitted from DNA to RNA to proteins, but not the other way round. Thanks to a recent technological revolution - the 'RNAissance' - it has, however, become clear that RNA is not solely a messenger for passing on the genetic information necessary for protein synthesis, but that RNA also plays an important role in sickness and health. In the past 5 years alone more than 100 therapies with (complementary) RNA molecules have been investigated in Phase 1 trials, and a quarter of these have also been investigated in Phase 2 or 3 trials. The dramatic increase in the number of pharmaceutical companies that are developing RNA therapeutics illustrates the enormous potential of these medicines. Once the toxicity and the costs of RNA therapeutics can be limited, these medicines - personalized or not - could soon be prescribed for patients with a wide range of chronic conditions.
Assuntos
Doença Crônica/terapia , Terapia Genética/métodos , Medicina de Precisão , RNA , Fenômenos Genéticos , Humanos , Biologia Molecular/tendênciasRESUMO
A 35-year-old man with a paraphilia was treated with long-acting gonadorelin. The desired result was reduced preoccupation with sexuality, but there were various side effects including a serious amount of bone loss. We believe that more attention should be given to the adverse effects of long-term treatment with triptorelin. In our view the drug regimen needs to be revised.
Assuntos
Hormônio Liberador de Gonadotropina/agonistas , Osteoporose/induzido quimicamente , Transtornos Parafílicos/tratamento farmacológico , Pamoato de Triptorrelina/efeitos adversos , Adulto , Densidade Óssea/efeitos dos fármacos , Humanos , Masculino , Resultado do Tratamento , Pamoato de Triptorrelina/uso terapêuticoRESUMO
Orbital cellulitis is a rare disease usually caused by sinusitis. Generally, the prognosis of both preseptal cellulitis and orbital cellulitis is favourable. Radiological distinction should be made between an orbital abscess and subperiosteal empyema. Theoretically, empyema is more accessible to antibiotics and, as it arises in a pre-existing anatomical space, it needs less aggressive treatment than an abscess. In contrast, the wall of an abscess created by the bacteria is scarcely permeable to antibiotics. Indications for surgical drainage should be based on clinical findings and not on Chandler's classification. Loss of vision, an unresponsive pupil or a densely packed orbit are indications for immediate surgical drainage. Drainage of an orbital abscess may speed up recovery.
Assuntos
Celulite Orbitária/diagnóstico , Doenças Orbitárias/diagnóstico , Abscesso/complicações , Abscesso/diagnóstico , Adolescente , Antibacterianos/uso terapêutico , Pré-Escolar , Drenagem/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Celulite Orbitária/etiologia , Doenças Orbitárias/etiologia , Estudos Retrospectivos , Sinusite/complicações , Sinusite/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: A higher risk of developing osteopenia/ osteoporosis has been seen in HIV-infected patients. We compared HIV-infected patients, all treated with combination antiretroviral therapy (cART), with a low bone mineral density (BMD) (T-score < -1) to those with a normal BMD (T-score > -1), examining the relation with T-cell activation and bone turnover markers (c-terminal telopeptide (CTX) and procollagen type 1 amino-terminal propeptide (P1NP)). METHODS: In this single visit pilot study, bone turnover markers, T-cell activation (CD38 + HLA - DR +) and senescence (CD57+) of T cells were measured in patients who had previously undergone dual energy X-ray absorptiometry scanning. RESULTS: All study participants (n = 16) were male, on cART, with a median age of 61 years (IQR 56-66). Nine patients had osteopenia/osteoporosis. When comparing the patients with osteopenia/osteoporosis with those with a normal BMD, no differences in activation and senescence were found. A relation was seen between higher bone formation (P1NP) and patients who were on cART for longer. The median length of cART use was 5.5 years (IQR 4.5-7.8), with all patients on nucleoside reverse transcriptase inhibitors, 88% on tenofovir, 63% on non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 38% on protease inhibitors. Osteopenia/osteoporosis was seen in 100% of the patients on protease inhibitors versus 30% of those on NNRTIs. CONCLUSION: This study did not find an association between activated T cells and BMD, thus did not explain the higher prevalence of osteopenia/osteoporosis in HIV-infected patients. Interestingly, this small pilot showed that cART might influence BMD, with a possible negative effect for protease inhibitors and a possible protective effect for NNRTIs. These results warrant further investigation.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Doenças Ósseas Metabólicas/imunologia , Infecções por HIV/imunologia , Osteoporose/imunologia , Linfócitos T/imunologia , Absorciometria de Fóton , Fatores Etários , Idoso , Densidade Óssea , Doenças Ósseas Metabólicas/epidemiologia , Doenças Ósseas Metabólicas/virologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Osteoporose/epidemiologia , Osteoporose/virologia , Projetos Piloto , Prevalência , Fatores de Risco , Linfócitos T/virologiaRESUMO
Vascular smooth muscle cells (SMCs) perform diverse functions and this functional heterogeneity could be based on differential recruitment of distinct SMC subsets. In humans, however, there is little support for such a paradigm, partly because isolation of pure human SMC subsets has proven difficult. We report the cloning of 12 SMC lines from a single fragment of human internal thoracic artery and the elucidation of 2 distinct cellular profiles. Epithelioid clones (n=9) were polygonal at confluence, 105+/-9 micrometer in length, and had a doubling time of 39+/-2 hours. Spindle-shaped clones (n=3) were larger (267+/-18 micrometer long, P<0.01) and grew slower (doubling time 65+/-4 hours, P<0.01). Both types of clones expressed smooth muscle (SM) alpha-actin, SM-myosin heavy chains, h-caldesmon, and calponin, but only spindle-shaped clones expressed metavinculin. Epithelioid clones displayed greater proliferation in response to platelet-derived growth factor-BB and fibroblast growth factor-2 and were more responsive to the migratory effect of platelet-derived growth factor-BB. Spindle-shaped clones showed more robust Ca(2+) transients in response to angiotensin II, histamine, and norepinephrine, crawled more quickly, and expressed more type I collagen. On serum withdrawal, spindle-shaped clones differentiated into a contraction-competent cell. A regional basis for diversity among SMCs was suggested by stepwise arterial digestion, which liberated small, SM alpha-actin-positive cells from the abluminal medial layers and larger SMCs from all layers. These results identify inherent SMC diversity in the media of the adult internal thoracic artery and suggest differential participation of SMC subsets in the regulation of human arterial behavior.
Assuntos
Artéria Torácica Interna/citologia , Músculo Liso Vascular/citologia , Actinas/metabolismo , Adulto , Angiotensina II/farmacologia , Becaplermina , Western Blotting , Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ligação a Calmodulina/metabolismo , Divisão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Tamanho Celular/efeitos dos fármacos , Células Cultivadas , Células Clonais , Meios de Cultura/farmacologia , DNA Complementar/genética , Fator 2 de Crescimento de Fibroblastos/farmacologia , Humanos , Cariotipagem , Proteínas dos Microfilamentos , Músculo Liso Vascular/química , Músculo Liso Vascular/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Fenótipo , Fator de Crescimento Derivado de Plaquetas/farmacologia , Proteínas Proto-Oncogênicas c-sis , Fatores de Tempo , CalponinasRESUMO
Fluorescently labelled ether phospholipid (1-O-alkyl/alkenyl-2-acyl- glycerophosphocholine) readily internalizes at low temperatures (2 degrees C) after insertion into the plasma membrane of cultured fibroblasts. This fate differs markedly from that of its diacyl phospholipid analogue, which remains associated with the plasma membrane under similar conditions. Analysis by thin-layer chromatography reveals that the translocation involves transfer of the intact ether phosphatidylcholine molecules. Relative to control cells, a 2-fold increase of ether phosphatidylcholine uptake was noted when plasmalogen deficient fibroblasts were used. Back-exchange experiments demonstrate that more than 60% of the cell-associated ether lipid is translocated within the cells, irrespective of the cell strain that was used. The potential mechanism by which the translocation process is accomplished is discussed.
Assuntos
Membrana Celular/metabolismo , Lipídeos de Membrana/metabolismo , Éteres Fosfolipídicos/metabolismo , Plasmalogênios/análise , Células Cultivadas , Condrodisplasia Punctata/metabolismo , Fibroblastos/metabolismo , Humanos , Microscopia de Fluorescência , Fosfatidilcolinas/metabolismo , TemperaturaRESUMO
The competitive S-adenosylmethionine decarboxylase (SAMdc; EC 4.1.1.50) inhibitor 4-amidinoindan-1-one 2'-amidinohydrazone (CGP 48664A) inhibits growth more effectively than the irreversible SAMdc inhibitor 5'-[[(Z)-4-amino-2-butenyl]methylamino]-5'-deoxyadenosine (AbeAdo), while having similar effects on polyamine contents. We hypothesized that growth inhibition by CGP 48664A is not merely accomplished by SAMdc inhibition. Concentration-related growth inhibitory effects of AbeAdo, CGP 48664A and methylglyoxal bis(guanylhydrazone) (MGBG) were investigated in L1210 cells that were additionally exposed to 10 microM AbeAdo. This concentration causes maximal growth inhibition, profound SAMdc inhibition and plateau polyamine contents. Almost complete inhibition of functional SAMdc activity by 10 microM AbeAdo was confirmed by demonstration of poor conversion of tetradeuterated spermidine to tetradeuterated spermine by gas chromatography-mass spectrometry. Increasing AbeAdo did not affect L1210 cell numbers, viability, nor polyamine contents. MGBG proved highly toxic. CGP 48664A did not affect L1210 polyamine contents, but cell numbers and viability decreased dose-dependently to 50% and 70% of control, respectively. We conclude that CGP 48664A inhibits L1210 growth not only through SAMdc inhibition, but also by an as yet poorly understood second effect with higher IC50. The alleged second effect of CGP 48664A appears important for its potent antitumor effect.
Assuntos
Adenosilmetionina Descarboxilase/antagonistas & inibidores , Amidinas/farmacologia , Antineoplásicos/farmacologia , Indanos/farmacologia , Animais , Divisão Celular/efeitos dos fármacos , Desoxiadenosinas/farmacologia , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Leucemia L1210 , Mitoguazona/farmacologia , Espermidina/metabolismo , Espermina/metabolismo , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
Anticoagulation during pregnancy is complicated because of potential risks for mother and foetus. Unfractionated or low-molecular-weight heparin is used for most anticoagulant indications. Its efficacy, however, in pregnant women with prosthetic heart valves is questioned, therefore coumarins are preferred for this indication. We studied long-term effects of prenatal coumarin-exposure on growth and on neurological, behavioural and cognitive development in 274 school-age children in comparison with 231 age-matched non-exposed controls. No major abnormalities were found. The exposed children had an increased risk for minor neurological dysfunction and for a low intelligence quotient (IQ below 80). The risk for a combination of two or more (minor) abnormalities was higher for the exposed children, RR = 7.6. We conclude that prenatal exposure to coumarins is associated with an increased risk for disturbances in development in school-age children. However, for the vast majority of children there is no clinical significant effect on growth and long-term development.
Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Anormalidades Múltiplas/induzido quimicamente , Anticoagulantes/efeitos adversos , Cumarínicos/efeitos adversos , Deficiências do Desenvolvimento/induzido quimicamente , Transtornos do Crescimento/induzido quimicamente , Inteligência/efeitos dos fármacos , Complicações Hematológicas na Gravidez/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal , Anormalidades Induzidas por Medicamentos/epidemiologia , Anormalidades Múltiplas/epidemiologia , Anticoagulantes/administração & dosagem , Anticoagulantes/farmacologia , Anticoagulantes/uso terapêutico , Criança , Comportamento Infantil/efeitos dos fármacos , Cognição/efeitos dos fármacos , Estudos de Coortes , Cumarínicos/administração & dosagem , Cumarínicos/farmacologia , Cumarínicos/uso terapêutico , Deficiências do Desenvolvimento/epidemiologia , Relação Dose-Resposta a Droga , Feminino , Feto/efeitos dos fármacos , Seguimentos , Idade Gestacional , Transtornos do Crescimento/epidemiologia , Humanos , Testes de Inteligência , Masculino , Troca Materno-Fetal , Exame Neurológico , Gravidez , Resultado da Gravidez , Puberdade/efeitos dos fármacos , RiscoRESUMO
Anticoagulation with coumarins is an effective therapy during pregnancy. Fetal exposure to coumarin derivatives during the first trimester, however, is associated with skeletal anomalies (warfarin or coumarin embryopathy). Information about long-term effects of prenatal coumarin exposure on the skeletal development is not available. We investigated growth and body proportions at school age of children exposed to coumarins in utero. A blind population-based cohort study was conducted on 307 exposed children and 267 non-exposed controls ages 8-15 years. The exposed cohort was based on a prospective registry of coumarin-treated pregnant women. Anthropometric data included height, weight, head circumference, and measurements to evaluate body proportions. The mean height of exposed children did not differ from that of the non-exposed children (mean difference 0.01 SD). In addition, no differences were found for the proportional measures. As a group, children exposed in the first trimester showed no evidence of growth impairment. Two children in this group, however, were born with signs of coumarin embryopathy and one of these displayed a deficit in height at school age. Long-term growth was not affected by a high cumulative dosage or exposure after the first trimester. We conclude that, when exposure during the first trimester is avoided, coumarin therapy during pregnancy has no demonstrable risk for the child's skeletal development.